Location and timing control of Pol2 promoter-proximal pausing

Kinetic Competition between Elongation Rate and Binding of NELF Controls Promoter-Proximal Pausing
Jian Li, Yingyun Liu, Ho Sung Rhee, Saikat Kumar B. Ghosh, Lu Bai, B. Franklin Pugh, David S. Gilmour

http://www.sciencedirect.com/science/article/pii/S1097276513003791

Several significant conclusions: 
First, core promoters of protein-coding genes throughout theDrosophila genome contain little or no open Pol II promoter complexes. Thus immediately after assembly of the transcription complex at the core promoter, Pol II rapidly initiates and elongates into a paused state that precludes assembly of a second polymerase into an initiation complex. snRNA genes encoding components of the spliceosome and the induced heat shock genes are exceptional in that open Pol II promoter complexes are evident on these genes. 
Second, the location of the pause can be altered by perturbing the kinetics of elongation or the levels of pausing factors, suggesting that the location of the pause depends on a kinetic competition between elongation and the binding of these factors. 
Third, GAF tips this kinetic competition in favor of pausing by recruiting NELF to the promoter.

DNA methylome changes along the maternal-to-zygotic transition

In this issue of Cell, two studies from Jiang et al. (pp. 773–784) and Potok et al. (pp. 759–772) generate genome-wide methylome maps of zebrafish gametes and early embryos. Surprisingly, the sperm methylome remains largely unchanged until zygotic genome activation, and the oocyte undergoes a series of methylation-demethylation reprogramming cycles to ultimately match the patterns of sperm.

Question: How the piRNA dynamics co-incide with the methylation dynamics during MZT?

Reprogramming the Maternal Zebrafish Genome after Fertilization to Match the Paternal Methylation Pattern p759

Magdalena E. Potok, David A. Nix, Timothy J. Parnell, Bradley R. Cairns

In Brief | Summary | Full Text

Sperm, but Not Oocyte, DNA Methylome Is Inherited by Zebrafish Early Embryos p773

Lan Jiang, Jing Zhang, Jing-Jing Wang, Lu Wang, Li Zhang, Guoqiang Li, Xiaodan Yang, Xin Ma, Xin Sun, Jun Cai, Jun Zhang, Xingxu Huang, Miao Yu, Xuegeng Wang, Feng Liu, Chung-I Wu, Chuan He, Bo Zhang, Weimin Ci, Jiang Liu

In Brief | Summary | Full Text

CTCF, new role in mediating alternative splicing

CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing

http://www.nature.com/nature/journal/v479/n7371/full/nature10442.html?WT.ec_id=NATURE-20111103

What the authors did is to compare transcriptome of wildtype with that of CTCF-depletion one in two cell lines; they found an alternative splicing event on exon 5 of gene CD45, which is included (or more likely to be included) in the wildtype comparing to the depletion. And the reduced inclusion is likely correlated with the binding of CTCF downstream of the exon (instead of upstream). They argued that the CTCF binding can promote the RNA Pol II pausing at the exon when it's not methylated. When it's methylated, the CTCF can not bind and therefore cannot pause the pol II at the exons, which result in exclusion of the exon.  That's the story. 

Several questions:

1. I know the anti-correlation of DNA methylation and CTCF binding, which has been shown by other papers. But how the methylation in the EXON can prohibit the CTCF binding DOWNSTREAM? I meant when they are not that close.
2. Even though they observed reduced inclusion in the CTCF-depletion transcriptome, how do they know it's caused by the DOWNSTREAM binding, not binding elsewhere? Can they mutate the binding site of CTCF in the wildtype and observe the same exon exclusion?

If it's true that CTCF is (and there will be a long list of) location-specific DNA-binding ‘splicing factors’, I would wonder how this is linked with the ChIA-PET data, which can track the long-range interaction points (physically) in the chromosome, like the DNA looping structure. A very straightforward question is: whether the alternative splicing events is also mediated by the looping event? This might be other side of the picture, where CTCF binding can form a loop which can 'loop' out exons.

Tech Note:
The mixture of isoforms (MISO) model was applied to RNA-seq data (Supplementary Table 3) to identify exons with a high probability of differential expression in response to CTCF depletion, as assessed by the Bayes factor confidence index³⁹.

Conservation of transcription factor binding events predicts gene expression across species

Conservation of transcription factor binding events predicts gene expression across species: "We show that (i) there is a significantly higher degree of conservation of TFBEs when the target gene is expressed in both species; (ii) there is increased conservation of binding events for groups of TFs compared to individual TFs; and (iii) conserved TFBEs have a greater impact on the expression of their target genes than non-conserved ones. These results link conservation of structural elements (TFBEs) to conservation of function (gene expression) and suggest a higher degree of functional conservation than implied by previous studies."

Interesting point!

It's also worthy to check the cross-cellline cases.

New public MySQL server

New public MySQL server

Posted on July 6, 2011 by stephen

Alongside our website, ensembl provides direct access to our databases through our public MySQL server ensembldb.ensembl.org and as of today, we are pleased to announce the availability of a second MySQL mirror hosted on the east coast of the US. The new server is running on Amazon Cloud with the hostname

useastdb.ensembl.org

it can be directly direct accessed with the mysql client using port 5306 and username anonymous.
eg.

mysql -h useastdb.ensembl.org -u anonymous -P5306

It may also be accessed through our perl API with the following registry incantation:

use Bio::EnsEMBL::Registry;
my $registry = 'Bio::EnsEMBL::Registry';
$registry->load_registry_from_db( -host => 'useastdb.ensembl.org',
                                  -user => 'anonymous');

useastDB will provide the current ensembl release alongside the previous on a rolling basis. This means that useastdb is currently hosting release 63 with 62 databases only, this will then become release 64 with 63 databases after our next release. Our full set of older releases will continue to to be hosted onensembldb.ensembl.org

We hope that our users enjoy the faster access to our data that this new MySQL mirror should provide.

Several things to share

It's not a very productive day today, but several things I've learned could be worthy to share.

• xtable: the R package which could export tables to LaTeX or HTML. 
• Ocean in Google Earth: This is very cool project (as I always think what Google do).  If I could have more spare time, I'd definitely like to learn all Google API and build some cool stuff. It can be a job. 
• Galápagos Islands(科隆群岛): I'm not sure this is the same island as Uncle Qi has dreamed for, but it's definitely worthy to go in one day in my life. Darwin once visited there and discovered the rare species like giant tortoises(?), which directly lead to his evolution theory. 

Research highlights : Nature Genetics : Nature Publishing Group

Research highlights : Nature Genetics : Nature Publishing Group: "Cancer epigenomics

Epigenetic alterations are known to be common in cancer, and comprehensive genomic maps of epigenomic alterations in cancer are eagerly anticipated. Now, Andrew Feber, Adrienne Flanagan, Stephan Beck and colleagues report a comparative DNA methylome analysis of peripheral nerve sheath tumors (Genome Res. published online, doi:10.1101/gr.109678.110, 1 February 2011). The authors used methylated DNA immunoprecipitation and next-generation sequencing to profile methylation in pools of genomic DNA from benign neurofibromas, malignant peripheral nerve sheath tumors (MPNSTs) and normal Schwann cells. Global hypomethylation is thought to be a common feature of tumors, but the authors found no evidence of global hypomethylation in the MPNSTs. However, they observed general loss of methylation of satellite repeats. Interestingly, regions of differential methylation between MPNSTs and normal Schwann cells were preferentially located in CpG island shores and in promoters not associated with CpG islands, but not in CpG islands themselves. Finally, the authors integrated their methylation data with published expression profiles of neurofibromas and MPNSTs. These analyses showed that the expression of genes located near differentially methylated regions located in CpG island shores and in non-CpG island promoters could discriminate between neurofibromas and MPNSTs. EN

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